作为针对mopox病毒复制的向策略,阻止氨酸克罗托尼和有氧糖解
Pengjun Wei1, Zongzheng Zhao2, Ruoqi Xu1
1Department of Microbiology, Nanjing Medical University, Nanjing, 211166, P. R. China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|October 27, 2025
概括
姆波克斯病毒 (MPXV) 通过其I3蛋白的lysinecrotonylation增强有氧糖解,劫持宿主细胞代谢. 抑制这一过程抑制了病毒复制,揭示了mpox.的潜在治疗点.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 2022年和2024年的mopox疫情凸显了了解mopox病毒 (MPXV) 复制机制的需要.
- 病毒感染通常涉及代谢重编程,但MPXV的特定代谢操纵是未知的.
研究的目的:
- 阐明MPXV操纵宿主细胞代谢进行病毒复制的机制.
- 根据MPXV的代谢劫持策略,确定mpox的潜在治疗点.
主要方法:
- 研究MPXV与宿主细胞代谢的相互作用,重点关注蛋白质修饰和代谢途径.
- 在机理学研究中使用了MYST基因组酸转移酶1 (MYST1) 和WD重复蛋白26 (WDR26).
- 使用药理抑制剂,如MC4033,2-脱氧-D-葡萄糖 (2-DG) 和二乙酸 (DCA) 来评估治疗潜力.
主要成果:
- MPXV通过其必不可少的I3蛋白的lysinecrotonylation劫持有氧糖解.
- MPXV对MYST1进行上调,MYST1催化I3的克罗化,防止WDR26的降解,并增强糖解.
- 药理上抑制MYST1或糖解抑制MPXV复制.
结论:
- MPXV采用一种新的依赖于克罗托尼लेशन的机制来重新编程宿主代谢以进行病毒传播.
- 氨酸化和有氧糖解被确定为mopox治疗的潜在治疗标.
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